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Safety and Tolerability of Adoptive Cell Therapy in Cancer

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Abstract

Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection. In recent years, some ACTs have produced unprecedented breakthrough responses: TIL therapy has moved from melanoma to solid tumor applications, TCR-engineered cells are developed for hematologic and solid tumors, and CAR-engineered T cells have received Food and Drug Administration (FDA) approval for the treatment of patients with certain B-cell malignancies. Although results are encouraging, to date, only a small percentage of patients with advanced malignancies can benefit from ACT. Besides ACT availability and accessibility, treatment-related toxicities represent a major hurdle in the widespread implementation of this therapeutic modality. The large variety of observed toxicities is caused by the infused cell product or as side effects of accompanying medication and chemotherapy. Toxicities can occur immediately or can be delayed. In order to render those highly promising therapeutic approaches safe enough for a wider pool of patients outside of clinical trials, an international consensus for toxicity management needs to be established.

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Authors and Affiliations

  1. Department of Oncology, Lausanne University Hospital, and Ludwig Institute for Cancer Research, University of Lausanne, 1066, Lausanne, Switzerland

    Benita Wolf, Stefan Zimmermann, Caroline Arber, Melita Irving, Lionel Trueb & George Coukos

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  1. Benita Wolf
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  2. Stefan Zimmermann
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  3. Caroline Arber
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  4. Melita Irving
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  5. Lionel Trueb
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  6. George Coukos
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Correspondence to George Coukos.

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Institutional Review Board approval was not required because this is a review of the literature.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Prof. George Coukos, Dr Lionel Trueb, Dr Stefan Zimmermann, Dr Benita Wolf, Dr Melita Irving and Prof. Carline Arber are co-investigators in Iovance and Kite Pharma sponsored clinical studies at CHUV, Lausanne. Prof. Caroline Arber receives royalties from Cell Medica. Prof. Carline Arber has one patent issued in the field of engineered T-cell therapies licensed to Cell Medica in 2016. Prof. Caroline Arber has two provisional patent applications filed in the field of engineered T-cell therapies. Prof. Caroline Arber received consulting fees from Kite/Gilead.

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The authors state that this work has not received any funding.

Additional information

Part of a theme issue on “Safety of Novel Anticancer Therapies: Future Perspectives”. Guest Editors: Rashmi R Shah, Giuseppe Curigliano.

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Wolf, B., Zimmermann, S., Arber, C. et al. Safety and Tolerability of Adoptive Cell Therapy in Cancer. Drug Saf 42, 315–334 (2019). https://doi.org/10.1007/s40264-018-0779-3

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